Metabolic Cerebral Imaging in Incipient Dementia (MCI-ID)

Early and Long-Term Value of Imaging Brain Metabolism

A brain PET scan is recognized as "reasonable and necessary" for some patients with "a recently established diagnosis of dementia" (Centers for Medicare and Medicaid Services, Decision Memo CAG-00088R, 2004), but evidence is less clear for patients having less severe cognitive problems. A substantial portion of such patients will develop Alzheimer's disease and other forms of dementia, which affect millions of people in the U.S., costing us over $100 billion annually. This project employs a prospective randomized protocol to determine whether PET scanning can help distinguish those patients with early Alzheimer's changes in their brains from those having other causes of cognitive impairment more accurately than is done with current clinical practices alone, and lead to earlier, more effective therapies which extend patients' abilities to think and function independently.

Study Overview

• Status: Completed
• Conditions: Dementia
• Intervention / Treatment: Procedure: FDG-PET brain scan

Detailed Description

People experiencing mild cognitive changes represent an epidemiologically major segment of the geriatric patient population. In the present proposal, we aim to measure how knowledge of cerebral metabolic information 1) influences working diagnoses and management of patients being evaluated for symptoms of early cognitive decline, and 2) impacts upon long-term clinical outcomes, particularly of subjects having metabolic patterns consistent with presence of Alzheimer's disease (AD)-like changes in their brains. A total of 710 patients suffering from documentable decline of cognitive function in the absence of overt dementia will be studied at nine U.S. institutions with extensive experience and infrastructure in place for the evaluation of Alzheimer's disease and related disorders, and for neuroimaging. In this prospective, investigation, subjects will undergo baseline neuropsychologic testing and neuroimaging with MRI and FDGPET. PET scan reports will be sealed and randomized with respect to whether they are released to patients' managing physicians at the time of interpretation, or two years after the time that scanning is performed.

Working diagnoses of managing physicians will be recorded, as will the treatment decisions made by the managing physicians and their patients. Cognitive abilities, functional status, utilization of healthcare resources, and other clinical and social contact parameters will be assessed every six months. Our major hypotheses are that among patients whose PET results are immediately conveyed to their referring physicians, diagnoses and management plans will be positively affected, leading to more effective utilization of healthcare resources and to maintenance of cognitive and functional abilities at a higher level. This project will also provide a rich source of data that can be used to address questions outside of its major focus (e.g., prognostic accuracy of volumetric MRI data used instead of, or in conjunction with, FDG-PET data; incremental predictive value of applying statistically parameterizing and/or quantifying software tools to imaging data).

• Study Type: Interventional
• Enrollment (Actual): 710
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90095-6942
      • UCLA Medical Center
    • Santa Monica, California, United States, 90404
      • Santa Monica-UCLA Medical Center
  • Florida
    • Sarasota, Florida, United States, 34239
      • Gene E. Myers Cardiac and Vascular Consultants
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Hospital
  • New York
    • Buffalo, New York, United States, 14214
      • University of Buffalo
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cognitive deficit and/or personality change is present, as observable by physician and/or close contact(s) of the patient; or in the absence of this, the patient provides a clear history of decline which the patient's physician deems to be reliable.
• If history or neurologic exam reveals findings suspicious for stroke, tumor, bleed, ictal activity, or hydrocephalus, then CT/MRI and appropriate neurological or neurosurgical consultation must have been obtained.
• Standard history, physical, and laboratory screen have been performed to identify possible presence of depression, substance abuse, malnourishment, medication effects and interactions, cardiopulmonary compromise, electrolyte/calcium imbalance, anemia, hypoxemia, infection, thyroid dysfunction, renal dysfunction, hepatic dysfunction, or glucose dysregulation.
• Any positive findings revealed in 2) or 3) above have been appropriately treated, wherever possible, but cognitive/behavioral deficit persists post-therapy.

Exclusion Criteria:

• Subjects under age 65 will not be recruited, in order to enhance the clinical relevance of the project by focusing on the age groups in whom serious concerns about early signs and symptoms of senile onset dementia are most typically emerging.
• Overt dementia, as discussed above.
• Cognitive dysfunction has impaired subject's ability to perform activities of daily living.
• Present or past history of thyroid disease (due to effects of both the disease and thyroid hormone replacement therapy on brain metabolism that we and others have begun to identify, but which remain incompletely characterized.)
• Claustrophobia or metal in body or other condition that would preclude PET or MRI from being acquired, or visual, auditory or motor deficits that would preclude accurate neuropsychological testing.
• Cholinesterase inhibition therapy already initiated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Experimental arm will have an immediate release of the PET report	Procedure: FDG-PET brain scan; The difference in the two arms' interventions is the time at which the FDG-PET brain scan information is available for the subjects' managing physicians. Experimental arms will have an immediate release of the PET report, while the Active Comparator arms will have a delayed release of 2 years.; Other Names: [F-18]FDG PET brain scan administered once to both arms
Active Comparator: 2; Active Comparator arm will have a delayed release of 2 years	Procedure: FDG-PET brain scan; The difference in the two arms' interventions is the time at which the FDG-PET brain scan information is available for the subjects' managing physicians. Experimental arms will have an immediate release of the PET report, while the Active Comparator arms will have a delayed release of 2 years.; Other Names: [F-18]FDG PET brain scan administered once to both arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change from baseline in neuropsychological (cognitive,functional) test results	baseline and 2 years
utilization of healthcare resources	baseline and 2 years
PET results, compared with working diagnoses made before and after time of PET	baseline and up to 2 years
rates of prescription of AD-specific therapies	baseline and 2 years

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Centers for Medicare and Medicaid Services
• Investigators: Principal Investigator: Daniel H Silverman, MD, PhD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: May 24, 2006
• First Submitted That Met QC Criteria: May 24, 2006
• First Posted (Estimate): May 25, 2006

Study Record Updates

• Last Update Posted (Actual): May 2, 2017
• Last Update Submitted That Met QC Criteria: May 1, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: dementia; Alzheimer's disease; PET; mild cognitive impairment; FDG
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Dementia
• Other Study ID Numbers: 02-10-079, 03-04-026